The combination of terbufos and nicosulfuron can interact synergistically in corn to produce severe crop injury. Field and greenhouse studies conducted at the University of Illinois indicate terbufos formulation and placement, soil organic matter content, and rainfall timing affect injury potential. Infurrow-applied terbufos caused more injury to corn than terbufos placed in a surface band when treated with nicosulfuron; the 15G formulation was more injurious than the 20CR formulation. Rainfall received less than seven days prior to nicosulfuron application can enhance crop injury between these pesticides. Terbufos and nicosulfuron applications reduced corn fresh weight by 75, 45, and 41% in soils containing 1, 3, and 5% organic matter, respectively.Experiments were conducted to determine the effect of terbufos on the uptake, translocation, and metabolism of nicosulfuron in corn. Terbufos increased $\lbrack\sp \rm C\rbrack$nicosulfuron uptake into corn leaves and was attributed to reduced epicuticular leaf wax deposition in terbufos treated plants. $\rm\sp C$ translocation out of the treated leaf increased in terbufos treated corn and $\lbrack\sp \rm C\rbrack$nicosulfuron metabolism decreased. The delay in herbicide metabolism associated with terbufos caused the nicosulfuron to reduce in vivo ALS activity to 3 and 20% at 24 h and 6 and 38% at 48 h, respectively, in 1 and 5% OM soils treated with terbufos.To determine the mechanism of this interaction, the effect of terbufos on the metabolism of nicosulfuron was studied in corn grown hydroponically and in corn microsomes. $\lbrack\sp \rm C\rbrack$Nicosulfuron metabolism was inhibited by 10 and 15% 24 h after application with 0.45 and 4.5 $\mu\rm M$ terbufos, respectively. Plants grown in the presence of the terbufos oxidative metabolites, terbufos sulfoxide (SO) and terbufos sulfone (SF), had 22 and 55% reductions in nicosulfuron metabolism, respectively, 24 h after herbicide application. In microsomal preparations, terbufos-SO and terbufos-SF severely inhibited cytochrome P450 mediated hydroxylation of nicosulfuron while terbufos had a lesser effect. Terbufos-SO and terbufos-SF reduced nicosulfuron tolerance in corn by inhibiting the cytochrome P450 monooxygenases involved in nicosulfuron hydroxylation.